Inhibition of KCa2 and Kv11.1 Channels in Pigs With Left Ventricular Dysfunction

Figures

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  Figure 1. Timelines for the atrially tachypaced (A-TP), SHAM1, and SHAM2 groups. DC, direct current cardioversion; CO, cardiac output measurement; Echo, echocardiography; AP14145, a dose of 20 mg/kg AP14145 infused over 60 min; Dofetilide, a dose of 0.1 mg/kg dofetilide infused over 15 min.

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  Figure 2. STVQT and STVRR before and after infusion of AP14145 and dofetilide. Left column (A, B): STVQT+RR from the atrially tachypaced (A-TP) pigs and the SHAM1 pigs. Right column (C, D): STVQT+RR from the SHAM2 pigs. Two outlier values were removed from the SHAM2 STVRR group.

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  Figure 3. QTcB and RR intervals. Left column (A, B): QTcB and RR intervals from the atrially tachypaced (A-TP) pigs and the SHAM1 pigs. Right column (C, D): QTcB and RR intervals from the SHAM2 pigs.

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  Figure 4. The number of premature ventricular complexes (PVCs) during the 15 min preceding the first infusion of test compound and after the end of AP14145 and dofetilide infusions, respectively. Left: the atrially tachypaced (A-TP) group. Middle: the SHAM1 group. Right: the SHAM2 group. The percentages of PVCs out of the total number of heartbeats within each period are also given in the graphs. Data were analyzed with a Friedman test followed by Dunn’s multiple comparisons test using the number of PVCs after the first infusion of test compound as the control. The adjusted p-values in the graphs are from Dunn’s test.

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  Figure 5. Top: cardiac output (CO) at baseline [60 min after cardioversion in the atrially tachypaced (A-TP) pigs] and immediately after infusion of each compound in the A-TP (A), the SHAM1 (B), and SHAM2 (C) groups. Bottom: stroke volume (SV) at baseline and immediately after infusion of each compound in the A-TP (D), the SHAM1 (E), and SHAM2 (F) groups. Repeated measures analyses were made with ANOVA in all groups. The data after the first infusion of test compound were used as the control.